Behavioral and biological phenotypes of alcohol abuse and alcoholism have been described, investigated and reported in the literature for decades. In contemporary experimental literature, there has been considerable effort toward discovering hereditary factors that are ultimately expressed phenotypically as predispositions or susceptibilities to alcohol abuse. Knowledge in this arena has been advanced considerably by research both in humans and in animal models of alcohol abuse and alcoholism but, in many cases, it has been difficult to draw meaningful parallels between the findings from human studies and that of animal research. This proposal focuses on an evaluation of the overall premise that the reinforcing effects of alcohol are reflected in, and are mediated partly by, phenotypic responses, and that these phenotypes include behavioral (e.g., locomotor) and autonomic activation. In recent studies, we have investigated heart rate (HR) as an index of autonomic activity that represents some distinctive profiles consequent to alcohol administration and alcohol ingestion (Bell et al., 2002). The proposed experiments seek to extend these findings and to test hypotheses concerning whether, and the extent to which, behavioral and HR reactions to alcohol's reinforcing properties result, at least in part, from hereditary predispositions to excessive alcohol self-administration. Another goal is to assess whether these phenotypic characterizations could prove to be useful, objective measures in evaluating theoretical assumptions on the behavioral and neurobiological substrates of alcohol's reinforcing efficacy, which could assist in pharmacotherapy development. To accomplish these goals, experiments in four Specific Aims will investigate in selectively bred rats (1) behavioral and HR dose-response effects of ethanol administration, (2) behavioral and HR activating effects of self-administered ethanol in free-choice drinking, (3) behavioral and HR activating effects of self-administered ethanol in an operant paradigm designed to evaluate periods of anticipation, extinction, and recovery of responding, and (4) behavioral and HR activating effects of intracranially self-administered ethanol directly into the ventral tegmental area of the brain in order to provide an evaluation of potential neurobiological substrates mediating these behavioral phenotypes. The findings will serve to evaluate, expand and validate the proposed measures as phenotypic associations within animal models of excessive alcohol-seeking behavior and will provide potential empirical parallels of characterized phenotypes in human alcoholics and those who are predisposed to alcohol abuse and alcoholism.